Men who have sex with men (MSM) are the largest HIV transmission group in the US and infections are increasing most among young MSM (18-24 years), however, few HIV prevention programs have been developed and proven effective with this vulnerable population. To address these HIV prevention concerns, we collaborated with community-based organizations (CBOs) in the context of an NIH R34 grant to develop and pilot test, Keep It Up! (KIU!), an online HIV prevention program tailored to ethnically diverse YMSM. KIU! is based on the Information-Motivation-Behavior Skills (IMB) model of HIV risk behavior change and informed by principals of E-learning. Our small-scale pilot randomized clinical trial (RCT) demonstrated the feasibility and acceptability of the KIU! intervention: we enrolled an ethnically diverse sample of YMSM; achieved excellent retention through 3-month follow-up (89%); maintained robust intervention engagement; and produced a significant 44% decrease in unprotected anal sex relative to an active control. The overarching goal of the current proposal is to advance scientific knowledge of technology-based, behavioral HIV prevention, as well as improve public health by establishing the efficacy of an innovative eHealth prevention program for YMSM. We will accomplish these goals with three specific aims. First, we will integrate the KIU! intervention into a widely-used health technology platform to increase its scalability, adaptability, and potential for broad implementation. Second, we will test the efficacy of the KIU! eHealth intervention in a multisite RCT by: a) enrolling ethnically diverse YMSM (N = 750; > 65% racial/ethnic minorities) who tested HIV negative in the clinics of our community partners in Chicago and New York; b) randomizing participants to either the KIU! intervention or an HIV knowledge control condition; and c) measuring intervention outcomes at baseline and follow-up assessments at 3, 6, and 12 months. The primary behavioral outcome will be the count of unprotected anal sex acts and the primary biomedical outcome will be STI incidence. And third, we will explore if the KIU! intervention has differential efficacy across important sub-groups of YMSM based on race/ethnicity, relationship status (serious versus casual relationships), and gay/bisexual identity. Our KIU! approach is innovative in linking an eHealth solution to HIV and STI testing, as well as serving as model for integrating scalable behavioral prevention into other biomedical prevention strategies. PUBLIC HEALTH RELEVANCE: Men who have sex with men (MSM) are the largest HIV transmission group in the US and infections are increasing most among young MSM (18-24 years), however, few HIV prevention programs have been developed and proven effective with this vulnerable population. The overarching goal of this proposal is to improve public health by establishing the efficacy of an innovative, Internet-based HIV prevention program for YMSM.